Influenza vaccines formulated as liquids can be subject to chemical degradation, e.g., aggregation, denaturation, hydrolysis, and oxidation that can result in their inactivation. Liquid vaccine formulations can also be sensitive to temperature: high temperatures can increase inactivation, and freezing temperatures can result in ice that can damage antigen in the vaccine. Thus, to prevent inactivation, liquid vaccines are often stored and distributed in a temperature range between 2 and 8 degrees C. Such storage can be costly, both for long-term storage and transportation of vaccines, and from loss of vaccine due to expiration. Generation of vaccines that are stable at room temperature would result in savings with respect to storage and would facilitate stockpiling. There is a need for means of generating vaccine formulations that are stable at room temperature, such as dry powder vaccines.
Several methods of freeze-drying vaccines have been described. For example, lyophilization (freeze-drying) of influenza vaccine solution can be used to generate a vaccine powder. However, the influenza vaccine powder produced by this method can be a hard cake, which does not facilitate consistent and reliable administration. Sprayfreeze-drying (SFD) of an influenza vaccine solution can provide fine particles of influenza vaccine powder; however, SFD is a high-cost method. Thus, there is a need for low-cost methods of generating fine powder vaccines with relatively high flowability and relatively low hygroscopicity.
The mode of administration of a vaccine can play a role in its efficacy. One mode of administration, nonparental administration (e.g., nasal), can induce and promote mucosal and systemic humoral and cell mediated immune responses. Mucosal vaccination can result in induction of secretory IgA (sIgA) responses in the respiratory tract and oropharyngeal region. One feature of mucosal sIgA antibodies is that they can provide cross-protection against antigenically distinct viruses; thus, mucosal sIgA responses have the potential to provide protection against a viral strain that has drifted from the strain used to generate the vaccine (for example, influenza virus H1N1 can drift to H2N1 or H1N2). Furthermore, sIgA can help bind a virus or other pathogen at the mucosal surface, preventing access of the pathogen to deeper tissues and/or decreasing the likelihood of full-blown infection. Described herein are novel methods for generating an sIgA inducing vaccine, for example, a powder vaccine formulation for nonparental administration.